Interaction of PAH-related compounds with the alpha and beta isoforms of the estrogen receptor

The ability of several 4- and 5-ring polycyclic aromatic hydrocarbons (PAHs ), heterocyclic PAHs. and their monohydroxy derivatives to interact with th e estrogen receptor (ER) alpha and beta isoforms was examined. Only compoun ds possessing a hydroxyl group were able to compete with H-3-labeled 17 bet a -estradiol(E2) for binding to either a glutathione-S-transferase and huma n ER alpha D, E, and F domain fusion protein (GST-hER alpha def) or to the full-length human ERP. Competitive binding was comparable for both isoforms , with IC,, values ranging from 20 to 300 nM (E2 IC50, approximately 3 nM). However, several compounds were able to induce reporter gene expression pr eferentially through mER beta, using MCF-7 cells transiently transfected wi th either a Ga14-human ER alpha def or Gal4-mouse ER beta def construct, as well as a Gal4-regulated reporter. These data extend the number and type o f PAM-related compounds capable of interacting with ER alpha and ER beta, a nd provides additional evidence that even though some compounds may possess a similar affinity for both ER isoforms. the capacity for transcriptional activation can still be isoform-specific. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.